Abstract
The intracellular receptor for thyroid hormone is a protein found in chromatin. Since thyroid hormone stimulates transcription of the growth hormone gene through an unknown mechanism, the hypothesis that the thyroid hormone-receptor complex interacts with defined regions of this gene has been investigated in a cell-free system. Nuclear extracts from human lymphoblastoid IM-9 cells containing thyroid hormone receptors were incubated with L-3,5,3'-tri[125I]iodothyronine and calf thymus DNA-cellulose. Restriction fragments of the human growth hormone gene were added to determine their ability to inhibit labeled receptor binding to DNA-cellulose. These fragments encompassed nucleotide sequences from about three kilobase pairs upstream to about four kilobase pairs downstream from the transcription initiation site. The thyroid hormone-receptor complex bound preferentially to the 5'-flanking sequences of the growth hormone gene in a region between nucleotide coordinates -290 and -129. The receptor also bound to an analogous promoter region in the human placental lactogen gene, which has 92% nucleotide sequence homology with the growth hormone gene. These binding regions appear to be distinct from those that are recognized by the receptor for glucocorticoids, which stimulate growth hormone gene expression synergistically with thyroid hormone. The presence of thyroid hormone was required for binding of its receptor to the growth hormone gene promoter, suggesting that thyroid hormone renders the receptor capable of recognizing specific gene regions.
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Selected References
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- Casanova J., Copp R. P., Janocko L., Samuels H. H. 5'-Flanking DNA of the rat growth hormone gene mediates regulated expression by thyroid hormone. J Biol Chem. 1985 Sep 25;260(21):11744–11748. [PubMed] [Google Scholar]
- Charles M. A., Ryffel G. U., Obinata M., McCarthy B. J., Baxter J. D. Nuclear receptors for thyroid hormone: evidence for nonrandom distribution within chromatin. Proc Natl Acad Sci U S A. 1975 May;72(5):1787–1791. doi: 10.1073/pnas.72.5.1787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crew M. D., Spindler S. R. Thyroid hormone regulation of the transfected rat growth hormone promoter. J Biol Chem. 1986 Apr 15;261(11):5018–5022. [PubMed] [Google Scholar]
- Diamond D. J., Goodman H. M. Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine. Transcriptional rate and mRNA stability changes in pituitary tumor cells. J Mol Biol. 1985 Jan 5;181(1):41–62. doi: 10.1016/0022-2836(85)90323-7. [DOI] [PubMed] [Google Scholar]
- Dobner P. R., Kawasaki E. S., Yu L. Y., Bancroft F. C. Thyroid or glucocorticoid hormone induces pre-growth-hormone mRNA and its probable nuclear precursor in rat pituitary cells. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2230–2234. doi: 10.1073/pnas.78.4.2230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
- Eliard P. H., Marchand M. J., Rousseau G. G., Formstecher P., Mathy-Hartert M., Belayew A., Martial J. A. Binding of the human glucocorticoid receptor to defined regions in the human growth hormone and placental lactogen genes. DNA. 1985 Dec;4(6):409–417. doi: 10.1089/dna.1985.4.409. [DOI] [PubMed] [Google Scholar]
- Evans R. M., Birnberg N. C., Rosenfeld M. G. Glucocorticoid and thyroid hormones transcriptionally regulate growth hormone gene expression. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7659–7663. doi: 10.1073/pnas.79.24.7659. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fried M. G., Crothers D. M. Equilibrium studies of the cyclic AMP receptor protein-DNA interaction. J Mol Biol. 1984 Jan 25;172(3):241–262. doi: 10.1016/s0022-2836(84)80025-x. [DOI] [PubMed] [Google Scholar]
- Ivarie R. D., Morris J. A., Eberhardt N. L. Hormonal domains of response: actions of glucocorticoid and thyroid hormones in regulating pleiotropic responses in cultured cells. Recent Prog Horm Res. 1980;36:195–239. doi: 10.1016/b978-0-12-571136-4.50012-7. [DOI] [PubMed] [Google Scholar]
- MacLeod K. M., Baxter J. D. Chromatin receptors for thyroid hormones. Interactions of the solubilized proteins with DNA. J Biol Chem. 1976 Dec 10;251(23):7380–7387. [PubMed] [Google Scholar]
- Martial J. A., Baxter J. D., Goodman H. M., Seeburg P. H. Regulation of growth hormone messenger RNA by thyroid and glucocorticoid hormones. Proc Natl Acad Sci U S A. 1977 May;74(5):1816–1820. doi: 10.1073/pnas.74.5.1816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore D. D., Marks A. R., Buckley D. I., Kapler G., Payvar F., Goodman H. M. The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor. Proc Natl Acad Sci U S A. 1985 Feb;82(3):699–702. doi: 10.1073/pnas.82.3.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nyborg J. K., Nguyen A. P., Spindler S. R. Relationship between thyroid and glucocorticoid hormone receptor occupancy, growth hormone gene transcription, and mRNA accumulation. J Biol Chem. 1984 Oct 25;259(20):12377–12381. [PubMed] [Google Scholar]
- Pfahl M. Specific binding of the glucocorticoid-receptor complex to the mouse mammary tumor proviral promoter region. Cell. 1982 Dec;31(2 Pt 1):475–482. doi: 10.1016/0092-8674(82)90140-4. [DOI] [PubMed] [Google Scholar]
- Samuels H. H., Stanley F., Shapiro L. E. Dose-dependent depletion of nuclear receptors by L-triiodothyronine: evidence for a role in induction of growth hormone synthesis in cultured GH1 cells. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3877–3881. doi: 10.1073/pnas.73.11.3877. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schwartz H. L., Surks M. I., Oppenheimer J. H. Quantitation of extrathyroidal conversion of L-thyroxine to 3,5,3'-triiodo-L-thyronine in the rat. J Clin Invest. 1971 May;50(5):1124–1130. doi: 10.1172/JCI106584. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selby M. J., Barta A., Baxter J. D., Bell G. I., Eberhardt N. L. Analysis of a major human chorionic somatomammotropin gene. Evidence for two functional promoter elements. J Biol Chem. 1984 Nov 10;259(21):13131–13138. [PubMed] [Google Scholar]
- Slater E. P., Rabenau O., Karin M., Baxter J. D., Beato M. Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene. Mol Cell Biol. 1985 Nov;5(11):2984–2992. doi: 10.1128/mcb.5.11.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spindler S. R., Mellon S. H., Baxter J. D. Growth hormone gene transcription is regulated by thyroid and glucocorticoid hormones in cultured rat pituitary tumor cells. J Biol Chem. 1982 Oct 10;257(19):11627–11632. [PubMed] [Google Scholar]
- Tsai J. S., Samuels H. H. Thyroid hormone action: demonstration of putative nuclear receptors in human lymphocytes. J Clin Endocrinol Metab. 1974 May;38(5):919–922. doi: 10.1210/jcem-38-5-919. [DOI] [PubMed] [Google Scholar]
- Yaffe B. M., Samuels H. H. Hormonal regulation of the growth hormone gene. Relationship of the rate of transcription to the level of nuclear thyroid hormone-receptor complexes. J Biol Chem. 1984 May 25;259(10):6284–6291. [PubMed] [Google Scholar]
